Maternal High Glucose and Fat Diet Exposure Impaired Vascular Constriction Via Mir-325-3p/ship2/nox2 Pathway Axis in Offspring Vessels

BACKGROUND AND OBJECTIVES:Maternal western-style diets that are high in glucose and fat have well-known cardiovascular effects on offspring, yet the combined influence of such diets during pregnancy is relatively less comprehended. This study investigates the impact of maternal high glucose and fat diet (HGF) on vascular constriction in offspring and the underlying mechanisms. METHODS AND RESULTS:Pregnant Sprague-Dawley rats were provided with either HGF or control diets. The assessment of fetal and postnatal vascular function disclosed an enhanced sensitivity to angiotensin II-induced vascular constriction in the offspring exposed to HGF. This was ascribed to increased oxidative stress via upregulated NOX2 expression, which was due to downregulated SHIP2 expression that was influenced by upregulated miR-325-3p. The maternal HGF diet elevated miR-325-3p, suppressed SHIP2 and enhanced NOX2 expression in fetal vascular tissues, thereby resulting in vascular dysfunction. These alterations persist into adulthood, heightening the risk of vascular diseases. CONCLUSION:The present study is the first to demonstrate that maternal HGF diet impairs vascular constriction function in offspring through the miR-325-3p/SHIP2/NOX2 pathway. These novel findings indicate that the detrimental effects of maternal HGF diet on fetal vascular function can persist into adulthood, advancing our knowledge on the impact of maternal diet on offspring vascular health and the early stages of fetal-origin vascular diseases.